Abstract: :
Purpose: Recently, we reported that antigen-specific NK thymocytes,(AC-Thyreg) are induced by dendritic cells that appear in theblood following the intracameral injection of antigen. In turn,AC-Thyreg activate immunoregulatory T cells (AC-SPL) in thespleens of immunized recipients. This study examines two newaspects of the induction of ACAID: (i) influence of a recipientsimmunizing antigen dose on the generation of ACAID or AC-SPLinduced by transferred AC-Thyreg,( ii) the influence of thesympathetic nervous system (SNS), which densely inervates theuvea, thymus and spleen, on the induction of ACAID.Methods:AC-Thyregwere obtained from Balb/c mice receiving intracameralTNP-BSA. AC-SPL were obtained from TNP-BSA-immunized mice oneweek following i.v. AC-Thyreg or intracameral injection of antigen.Mice were chemically sympathetomized two days before systemicimmunization by the ip injection of 6-hyroxydopamine (6-OHDA)which destroys peripheral SNS axons. Control mice received theantagonist desipramine with 6-OHDA. DTH to TNP was measuredby swelling of a footpad 24hr after epicutaneous challenge withpicryl chloride (PCl). Anti-TNP antibodies were measured byELISA. Splenic immunoregulatory effector cells were measuredby the injection of AC-SPL into the footpad immediately afterepicutaneous challenge with PCl.Results: AC-Thyreg from micereceiving intracameral TNP-BSA induced AC-SPL cells in recipientsimmunized systemically with TNP-BSA but not in naive mice ormice immunized with BSA or ovalbumin. ACAID ( measured as thesuppression of DTH and the enhanced production of IgG1 antibodiesspecific for the intracameral antigen) was induced in mice immunizedwith 200µg of TNP-BSA but not in mice immunized with 20µgTNP-BSA. DTH was not expressed but IgM antibody production wasenhanced in mice sympathectomized by the injection of 6-OHDA.Splenic immunoregulatory effector cells or AC-Thyreg were notrecovered from sympathectomized mice receiving intracameralantigen. All of the sympathectomy effects were abrogated incontrol mice receiving desipramine in addition to 6-OHDA.Conclusions:The results provide additional evidence suggesting that immunedeviation and the generation of splenic immunoregulatory T cellsin ACAID depends on systemic immunzation. An intact sympatheticnervous system, (known to influence cell-mediated and humoralimmunity), is required to generate AC-Thyreg and splenic immunoregulatoryeffector T cells in ACAID.